Prahran MP Sam Hibbins has announced he is quitting the Victorian parliament three weeks after leaving the Greens party room because of an affair with a staffer.

In a statement on Saturday, Mr Hibbins said he had made the decision for the sake of his family's "well-being and safety".

On November 1, Mr Hibbins, who is married with two children, went from being co-deputy leader of the Victorian Greens to an independent MP because a short-lived extra-marital relationship he had had breached party rules.

His departure from state parliament means the seat of Prahran will go to a by-election.

It is a significant electorate for the Victorian Greens, who have held the inner south-east Melbourne seat for 12 years — since Mr Hibbins won it in 2014.

However on Saturday Mr Hibbins said recent weeks had made it clear he had to prioritise his family's wellbeing.

"It has been an extremely difficult time for us as the public disclosure of what was a private matter has taken a significant toll on our family's mental health," he wrote.

"Deeply distressingly, following my resignation from the Greens, there was unauthorised access to my office [in] Parliament House.

"Personal items, including family and my children's baby photos, were vandalised with offensive and threatening graffiti. We believe this involved a number of people.

"This has become a concerted campaign against me.

"I will be formally resigning as the Member for Prahran and from the Victorian Parliament."

He told the ABC he was informed of the vandalism inside his office by parliamentary services on November 11.

"I have reported the matter to police and will be providing them with further details as per their request," he said.

Victoria Police said on Saturday afternoon it would need more specific information about the incident to confirm whether it had been reported.

Victorian Greens leader Ellen Sandell said she supported Mr Hibbins's decision to resign from the parliament.

"As I have previously said, the Member for Prahran's actions do not meet the standard of behaviour we expect from our MPs, which is why we took strong action to remove him from our Greens party room. I'm glad he has now also resigned from parliament," she said.

A Prahran by-election presents an unusual contest, with the Greens, Labor and Liberals all having held the seat at various times in the past two decades.

It will provide a mid-term litmus test of how both major party leaders are faring as well as the strength of the Greens in inner Melbourne.